A catalytic asymmetric intramolecular homologation of simple ketones with α-diazoesters was firstly accomplished with a chiral N,N′-dioxide–Sc(OTf)₃ complex. This method provides an efficient access to chiral cyclic α-aryl/alkyl β-ketoesters containing an all-carbon quaternary stereocenter. Under mild conditions, a variety of aryl- and alkyl-substituted ketone groups reacted with α-diazoester groups smoothly through an intramolecular addition/rearrangement process, producing the β-ketoesters in high yield and enantiomeric excess.

A catalytic asymmetric dearomatization of 2-naphthols with azodicarboxylates has been accomplished by using a N,N′-dioxide-scandium(III) complex as a chiral catalyst. A number of optically active β-naphthalenone compounds with a nitrogen-containing quaternary carbon stereocenter were obtained in up to 99 % yield and up to 99 % ee under mild reaction conditions. The reaction could be scaled up to a gram-scale with the yield and ee maintained. Based on these experiments and on previous reports, a possible transition state was proposed.

A highly efficient N,N′-dioxide–Ni^II catalyst system for the catalytic [3+2] cycloaddition of indoles with epoxides through CC cleavage of oxiranes was accomplished under mild conditions. It provided a promising approach for chiral furo[3,4-b]indoles in up to 98 % yield with up to 91 % enantiomeric excess (ee) and >95:5 diastereomeric ratio (d.r.).

The first example of a N,N′-dioxide–Sc^III-catalyzed 1,6-addition of 3-substituted oxindoles to dienyl ketones has been developed. This procedure tolerates a relatively wide range of 3-substituted oxindoles under mild conditions, facilitating the preparation of various chiral oxindoles with quaternary stereocenters. In addition, the reliable catalyst was found to be effective in the asymmetric 1,6-addition of both δ-unsubstituted and δ-methyl-substituted dienyl ketones, achieving excellent regioselectivities and enantioselectivities (up to>99 % ee).

An asymmetric synthesis of cyclic sulfamates by catalytic haloaminocyclization of primary sulfamate ester derivatives is described. The remarkable reversal of diastereoselectivity was found to be dependent on the halogen source and the chiral catalyst. By using privileged complexes of N,N′-dioxides with Sc(OTf)₃ or Lu(OTf)₃ as the catalyst, a variety of enantioenriched syn- and anti-cyclic sulfamates or related trans-aziridines could be obtained in 92–99 % ee and up to 97 % yield.

A highly enantioselective Mannich reaction of silyl ketene imines with isatin-derived ketimines has been realized by using a chiral N,N′-dioxide/Zn^II catalyst. A variety of β-amino nitriles containing congested vicinal tetrasubstituted stereocenters were obtained with excellent outcomes (up to 98 % yield, >19:1 d.r. and 99 % ee). Based on the experimental investigations, a possible transition state has been proposed to explain the origin of the asymmetric induction.

A catalytic asymmetric intramolecular homologation of simple ketones with α-diazoesters was firstly accomplished with a chiral N,N′-dioxide–Sc(OTf)₃ complex. This method provides an efficient access to chiral cyclic α-aryl/alkyl β-ketoesters containing an all-carbon quaternary stereocenter. Under mild conditions, a variety of aryl- and alkyl-substituted ketone groups reacted with α-diazoester groups smoothly through an intramolecular addition/rearrangement process, producing the β-ketoesters in high yield and enantiomeric excess.

The asymmetric ring-opening/cyclization of cyclopropyl ketones with primary amine nucleophiles was catalyzed by a chiral N,N′-dioxide/scandium(III) complex through a kinetic resolution process. A broad range of cyclopropyl ketones and primary amines are suitable substrates of this reaction. The corresponding products were afforded in excellent enantioselectivities and yields (up to 97 % ee and 98 % yield) under mild reaction conditions. This method provides a promising access to chiral 2,3-dihydropyrroles as well as an effective procedure for the kinetic resolution of 2-substituted cyclopropyl ketones.

A highly enantioselective Mannich reaction of silyl ketene imines with isatin-derived ketimines has been realized by using a chiral N,N′-dioxide/Zn^II catalyst. A variety of β-amino nitriles containing congested vicinal tetrasubstituted stereocenters were obtained with excellent outcomes (up to 98 % yield, >19:1 d.r. and 99 % ee). Based on the experimental investigations, a possible transition state has been proposed to explain the origin of the asymmetric induction.

The direct functionalization of sp³ CH bonds through a tandem 1,5-hydride shift/ring closure is described. Various optically active spirooxindole tetrahydroquinoline derivatives bearing contiguous quaternary or tertiary stereogenic carbon centers were readily synthesized. A chiral scandium complex of N,N′-dioxide promoted the reactions in good yields (up to 97 %) with excellent diastereoselectivities (>20:1) and enantioselectivities (up to 94 % ee). Kinetic isotope effect (KIE) experiments and internal redox reactions of chiral substrates were conducted, and the results provided intriguing information that helped clarify the mechanism of the reaction.

Highly efficient catalytic asymmetric Claisen rearrangements of O-propargyl β-ketoesters and O-allyl β-ketoesters have been accomplished under mild reaction conditions. In the presence of the chiral N,N′-dioxide/Ni^II complex, a wide range of allenyl/allyl-substituted all-carbon quaternary β-ketoesters was obtained in generally good yield (up to 99 %) and high diastereoselectivity (up to 99:1 d.r.) with excellent enantioselectivity (up to 99 % ee).

A simple and efficient acylative kinetic resolution of racemic mandelic acid esters was accomplished with a chiral N,N’-dioxide–scandium(III) complex under mild and base-free reaction conditions. A variety of mandelic acid esters performed well in the reaction, obtaining both acylated products (up to 49% yield, 97% ee) and recovered substrates (up to 49% yield, 95% ee) in high enantioselectivities with perfect selectivity factors (up to 247). The enantioselective recognition and catalytic models were also proposed for the catalytic KR reaction.

N,N′-Dioxide/nickel(II) complexes have been developed to catalyze the inverse-electron-demand hetero-Diels–Alder reaction of β,γ-unsaturated α-ketoesters with acyclic enecarbamates. After detailed screening of the reaction parameters, mild optimized reaction conditions were established, affording 3,4-dihydro-2H-pyranamines in up to 99 % yield, 99 % ee and more than 95:5 d.r. The catalytic system was also efficient for β-substituted acyclic enecarbamates, affording more challenging 2,3,4-trisubstituted 3,4-dihydro-2H-pyranamine with three contiguous stereogenic centers in excellent yields, diastereoselectivities, and enantioselectivities. The reaction could be scaled up to a gram scale with no deterioration of either enantioselectivity or yield. Based on these experiments and on previous reports, a possible transition state was proposed.

A highly enantioselective hetero-Diels–Alder reaction of Danishefsky’s diene with α-ketoesters and isatins has been realized by using a chiral N,N′-dioxide/Mg^II complex. In the presence of only 0.1–0.5 mol % catalyst, a series of substrates were transformed into the corresponding tetrasubstituted 2,3-dihydropyran-4-ones in up to 99 % yield and more than 99 % ee in two hours.

An efficient enantioselective reduction of α-amino ketones with potassium borohydride solution catalyzed by chiral N,N′-dioxide–metal complex catalysts was accomplished under mild reaction conditions for the first time. It provided a simple, convenient, and practical approaches for obtaining synthetically important chiral β-amino alcohols in good to excellent yields (up to 98 %) and enantioselectivities (up to 97 % ee).

Efficient enantioselective NH insertion reactions of secondary and primary anilines were catalyzed by palladium(0) in combination with chiral guanidine derivatives. A broad range of substituted anilines were tolerated, and the corresponding products were obtained in high yield (up to 99 %) with good enantioselectivity (up to 94 % ee) under mild reaction conditions. The NH insertion mechanism was examined by the study of kinetic isotope effects, control experiments, HRMS, and spectroscopic analysis.

Highly efficient catalytic asymmetric Claisen rearrangements of O-propargyl β-ketoesters and O-allyl β-ketoesters have been accomplished under mild reaction conditions. In the presence of the chiral N,N′-dioxide/Ni^II complex, a wide range of allenyl/allyl-substituted all-carbon quaternary β-ketoesters was obtained in generally good yield (up to 99 %) and high diastereoselectivity (up to 99:1 d.r.) with excellent enantioselectivity (up to 99 % ee).

Chiral N,N′-dioxide/Zn(NTf₂)₂ complexes were demonstrated to be highly effective in the direct asymmetric conjugate addition of arylacetonitriles to alkylidene malonates under mild conditions. A wide range of substrates were tolerated to afford their corresponding products in moderate-to-good yields with high diastereoselectivities (82:18–>99:1 d.r.) and enantioselectivities (81–99 % ee). The reactions performed well, owing to the high Lewis acidity of the metal triflimidate and a ligand-acceleration effect. The N,N′-dioxide also benefited the deprotonation process as a Brønsted base. The catalytic reaction could be performed on the gram-scale with retention of yield, diastereoselectivity, and enantioselectivity. The products that contained functional groups were ready for further manipulation. In addition, a possible catalytic model was proposed to explain the origin of the asymmetric induction.

The highly Z-selective asymmetric conjugate addition of 3-substituted oxindoles to alkynyl carbonyl compounds has been developed by using scandium complexes of chiral N,N′-dioxides under mild conditions. The thermodynamically unstable Z-olefin derivatives were obtained in excellent yields and high enantiomeric and geometric control. The catalyst was also found to be effective in the asymmetric acetylenic substitution reaction of 3-substituted oxindoles, giving excellent enantioselectivities.

The asymmetric Kinugasa reaction was performed on pure water for the first time without the need for any organic co-solvents. In contrast to most asymmetric Kinugasa reactions, trans-β-lactams were obtained as the major products in good yields, enantioselectivities, and diastereoselectivities (up to 90 % yield, 98 % ee, and >99:1 d.r.). This reaction is atom-economical, environmentally friendly, and affords synthetically useful but challenging products.

We demonstrated an asymmetric 1,3-dipolar cycloaddition of azomethine betaines with alkylidene malonates by using a chiral N,N′-dioxide–Ni^II complex as a catalyst. Both aromatic- and aliphatic-substituted alkylidene malonates were found to be suitable for the reaction. A range of trans-pyrazolone derivatives was exclusively obtained with excellent yields (up to 99 % yield) and good enantioselectivities (up to 97 % ee) under mild reaction conditions. The reaction could be carried out on a gram scale with the good results being maintained. Control experiments were performed to elucidate the specific diastereoselectivity of the reaction. The formation of single trans isomers was dominated by secondary orbital interactions between the ester groups of the dipolarophile and the azomethine imine. On the basis of the experimental results and previous reports, a possible catalytic model was assumed.

A highly enantioselective Friedel–Crafts reaction of activated phenols with (E)-4-oxo-4-arylbutenoates has been developed with the N,N′-dioxide-scandium(III) complex as the catalyst. A variety of (E)-4-oxo-4-arylbutenoates were found to be suitable substrates for the reaction. The desired products were obtained in moderate to high yields (up to 98%) and excellent enantioselectivities (up to 97% ee).

An exploration of the mechanism of the aminolysis of meso-epoxides catalyzed by the proline-based N,N′-dioxide-indium tris(triflate) complex was performed using control experiments, UV-Vis spectroscopy, ¹H NMR, electrospray ionization mass spectrometry (ESI-MS) and scanning electron microscopy (SEM). Control experiments disclosed that the ligand-to-indium tris(triflate) ratio, the catalyst loading, the concentration, and the presence of 4 Å MS have dramatic effects on this reaction with regard to both the yield and the enantioselectivity. Combined with control experiments, UV-Vis spectroscopy, ¹H NMR, ESI-MS and SEM analyses revealed that molecular sieves perform multiple functions in the catalysis. A plausible molecular sieves-assisted reaction pathway was proposed. In this pathway, molecular sieves perform (i) as desiccant to in situ dry the reaction system, (ii) as proton transfer agent to accelerate the catalysis, and (iii) as counter ion source to preserve the electroneutrality of the transition states. Besides, the generality of the substrate scope was further explored; excellent yields (up to 99%) and enantioselectivities (up to 99% ee) were obtained.

Chiral 2-substituted-1,5-benzodiazepine derivatives were synthesized for the first time from an enantioselective domino reaction involving o-phenylenediamine and 2′-hydroxychalcones. The titanium complex formed from chiral ligand 1a derived from (S)-BINOL and L-prolineamide promoted the reaction and gave the products in good yields with up to 82 % ee.

The N,N′-dioxide–Sc(OTf)₃ complex was applied in the asymmetric Michael reaction of 1H-benzotriazole with chalcones to give the corresponding N-1 products in excellent yields (up to 99 %) with excellent enantioselectivities (up to 99 % ee). Further transformation into other optically active derivatives such as β-benzotriazolyl ester, alcohol, and amide were also realized with excellent results.

The asymmetric synthesis of 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromene derivatives was achieved through a tandem Michael addition–cyclization reaction of easily available cyclohexane-1,3-dione and ethyl 2-cyano-3-phenylacrylates. Moderate to good yields (up to 81 %) and high enantioselectivities (up to 89 % ee) were obtained with a chiral salen–cobalt(II) complex. This process was air tolerant and easily performed, which provides an efficient method for the synthesis of chiral 4H-chromene derivatives.

Highly diastereo- and enantioselective iodoamination of chalcones, 4-aryl-4-oxobutenoates, and a trifluoro-substituted enone has been accomplished in the presence of a chiral N,N′-dioxide/[Sc(OTf)₃] complex (0.5–2 mol %), delivering the desired vicinal anti-α-iodo-β-amino carbonyl compounds regioselectively in high yields (up to 97 %) and with excellent diastereoselectivities (>99:1 d.r.) and enantioselectivities (up to 99 % ee). Enantiopure syn-α-iodo-β-amino products could also be obtained from the isomerization of particular iodo compounds. TsNHX species (X=Cl, Br, I), generated from the reactions between the halo sources and TsNH₂, were further confirmed as the active species in the haloamination reactions involved in the formation of the key halonium ion intermediates. A typical haloamination dependency was observed, with reactivity decreasing in the order NBS>NIS≫NCS.

The asymmetric Povarov reaction with α-alkyl styrenes as dienophiles was catalyzed by an N,N′-dioxide L4–Sc(OTf)₃ complex. Enantiopure tetrahydroquinoline derivatives with a quaternary stereocenter at the C4 position were synthesized for the first time. A wide variety of α-alkyl styrenes and N-aryl aldimines were tolerated in the reaction, to give excellent diastereo- (up to 99:1 d.r.) and enantioselectivities (92 to >99 % ee). In addition, the reaction could be performed on the gram scale without any loss of yield, diastereoselectivity, or enantioselectivity. An intermolecular hydrogen-shift reaction was found to be a side reaction, which offered a method to synthesize the corresponding quinoline derivatives with chiral quaternary sterocenters.

The asymmetric inverse-electron-demand hetero-Diels–Alder (HDA) reactions of β,γ-unsaturated α-ketoesters with electron-rich alkenes were investigated, with an N,N′-dioxide/erbium(III) complex employed as the catalyst. Quantitative conversion of the β,γ-unsaturated α-ketoesters and excellent enantioselectivities (up to >99 % ee) and diastereoselectivities (up to >99:1 d.r.) were observed for a broad range of substrates by using a 0.5–0.05 mol % catalyst loading under mild reaction conditions. The reaction could be scaled up to the gram scale with the same results. In addition, this was the first application of Er(OTf)₃ to the asymmetric inverse-electron-demand HDA reaction and it behaved as an efficient catalyst. Moreover, the synthetic utility of this methodology was demonstrated with the synthesis of key intermediates of some natural products.

The asymmetric three-component vinylogous Mannich reaction of an acyclic silyl dienol ester, an aldehyde and 2-aminophenol was accomplished using a chiral N,N′-dioxide-scandium(III) complex as the catalyst. A variety of aldehydes were found to be suitable substrates for the reaction and the desired δ-amino-α,β-unsaturated esters were obtained in 90–99% yields with good to excellent enantioselectivities (up to >99% ee) and complete regioselectivities. Moreover, the simple experimental procedures were air-tolerant and convenient. The present catalytic process provides the potential for large-scale syntheses of the chiral δ-amino-α,β-unsaturated esters.

A highly enantioselective Friedel–Crafts alkylation of indoles with ethyl trifluoropyruvate has been developed using N,N′-dioxide-zinc(II) complexes. Both enantiomers of the desired adducts were obtained by the use of enantiomeric ligands in excellent results (up to 99% yield and 98% ee) within 0.5 h under mild conditions. On the basis of the experimental results, a proposed working model was proposed to explain the origin of the asymmetric induction.

The catalytic enantioselective cyanation of aldehydes and ketones has received growing attention because the resulting enantiomerically pure cyanohydrins are versatile building blocks for many biologically active compounds. To date, both metal-based and organic catalysts have been successfully developed to promote these reactions enantioselectively. Great advances have been made in the catalytic enantioselective addition of various cyanide sources to carbonyl compounds. In this microreview, recent progress, including substrate scope and limitations, and probable reaction mechanisms are discussed. In addition, the application of this methodology to the synthesis of natural products is also presented briefly where appropriate.

A highly enantioselective α-amination of 3-substituted oxindoles with azodicarboxylates catalyzed by a chiral Sc(OTf)₃/N,N′-dioxide complex (Tf: triflate) has been developed and affords the corresponding 3-amino-2-oxindole derivatives in high yields (up to 98 %) with excellent enantioselectivities (up to 99 % ee). The procedure is capable of tolerating a relatively wide range of substrates, and excellent results (92–96 % ee) can also be obtained, even in the presence of 0.5 mol % of catalyst loading under mild conditions. These results showed the potential value of the catalytic approach. Moreover, with high synthetic versatility, the product could be easily transformed into optically active 3-amino-3-methyloxindole bearing a chiral quaternary stereogenic center.

Highly enantioselective Diels–Alder (DA) and inverse-electron-demand hetero-Diels–Alder (HDA) reactions of β,γ-unsaturated α-ketoesters with cyclopentadiene catalyzed by chiral N,N′-dioxide–Cu(OTf)₂ (Tf=triflate) complexes have been developed. Quantitative conversion of β,γ-unsaturated α-ketoesters and excellent diastereoselectivities (up to 99:1) and enantioselectivities (up to >99 % ee) were observed for a broad range of substrates. Both aromatic and aliphatic β,γ-unsaturated α-ketoesters were found to be suitable substrates for the reactions. Moreover, the chemoselectivity of the DA and HDA adducts were improved by regulating the reaction temperature. Good to high chemoselectivity (up to 94 %) of the DA adducts were obtained at room temperature, and moderate chemoselectivity (up to 65 %) of the HDA adducts were achieved at low temperature. The reaction also featured mild reaction conditions, a simple procedure, and remarkably low catalyst loading (0.1–1.5 mol %). A strong positive nonlinear effect was observed.

A highly enantioselective Friedel–Crafts (F–C) alkylation of indoles and pyrrole with chalcone derivatives catalyzed by a chiral N,N′-dioxide–Sc(OTf)₃ complex has been developed that tolerates a wide range of substrates. The reaction proceeds in moderate to excellent yields and high enantioselectivities (85–92 % enantiomeric excess) using 2 mol % (for indole) or 0.5 mol % (for pyrrole) catalyst loading, which showed the potential value of the catalyst system. Meanwhile, a strong positive nonlinear effect was observed. On the basis of the experimental results and previous reports, a possible working model is proposed to explain the origin of the activation and asymmetric induction.

A direct catalytic asymmetric aldol-type reaction of 3-substituted-2-oxindoles with glyoxal derivatives and ethyl trifluoropyruvate, catalyzed by a chiral N,N′-dioxide–Sc(OTf)₃ (Tf=trifluoromethanesulfonyl) complex, has been developed that tolerates a wide range of substrates. The reaction proceeds in good yields and excellent enantioselectivities (up to 93 % yield, 99:1 diastereomeric ratio (dr), and >99 % enantiomeric excess (ee)) under mild conditions, to deliver 3-(α-hydroxy-β-carbonyl) oxindoles with vicinal quaternary–tertiary or quaternary–quaternary stereocenters. Even with 1 mol % catalyst loading or on scaleup (10 mmol of starting material), maintenance of ee was observed, which showed the potential value of the catalyst system. In studies probing the reaction mechanism, a positive nonlinear effect was observed and Sc^III-based enolate intermediates were detected by using ESIMS. On the basis of the experimental results and previous reports, a possible catalytic cycle was assumed.

Highly enantioselective Michael addition of 1,3-dicarbonyl compounds and nitromethane to 4-oxo-4-arylbutenoates catalyzed by N,N′-dioxide–Sc(OTf)₃ complexes has been developed. Using 0.5–2 mol % catalyst loading, various α-stereogenic esters were obtained regioselectively with excellent yields (up to 97 %) and enantioselectivities (up to >99 % ee). Moreover, the reaction performed well under nearly solvent-free conditions. The products with functional groups are ready for further transformation, which showed the potential value of the catalytic approach. According to the experimental results and previous reports, a plausible working model has been proposed to explain the origin of the activation and the asymmetric induction.

An easily available and efficient chiral N,N′-dioxide–nickel(II) complex catalyst has been developed for the direct catalytic asymmetric aldol reaction of α-isothiocyanato imide with aldehydes which produces the products in morderate to high yields (up to 98 %) with excellent diastereo- (up to >99:1 d.r.) and enantioselectivities (up to >99 % ee). A variety of aromatic, heteroaromatic, α,β-unsaturated, and aliphatic aldehydes were found to be suitable substrates in the presence of 2.5 mol % L-proline-derived N,N′-dioxide L5–nickel(II) complex. This process was air-tolerant and easily manipulated with available reagents. Based on experimental investigations, a possible transition state has been proposed to explain the origin of reactivity and asymmetric inductivity.

A Lewis acid catalyst has been first applied to the hydrophosphonylation of ketones, giving the corresponding quaternary α-hydroxy phosphonates in high yields (up to 98%). The present method was highly tolerable for functionalized ketones. Moreover, the first catalytic enantioselective hydrophosphonylation of an unactivated ketone was also realized by using a tridentate Schiff base-titanium complex.

A type of C₂-symmetric secondary amine amide catalysts were developed for the asymmetric Michael addition of 4-hydroxycoumarin to α,β-unsaturated ketones. A series of important biologically and pharmaceutically active compounds were obtained in excellent yields (up to 99 %) with high enantioselectivities (up to 89 % ee) under mild conditions. In addition, enantiopure product could be obtained by a single recrystallization. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Full investigation of cyanation of aldehydes, ketones, aldimines and ketimines with trimethylsilyl cyanide (TMSCN) or ethyl cyanoformate (CNCOOEt) as the cyanide source has been accomplished by employing an in situ generated catalyst from cinchona alkaloid, tetraisopropyl titanate [Ti(OiPr)₄] and an achiral modified biphenol. With TMSCN as the cyanide source, good to excellent results have been achieved for the Strecker reaction of N-Ts (Ts=p-toluenesulfonyl) aldimines and ketimines (up to >99 % yield and >99 % ee) as well as for the cyanation of ketones (up to 99 % yield and 98 % ee). By using CNCOOEt as the alternative cyanide source, cyanation of aldehyde was accomplished and various enantioenriched cyanohydrin carbonates were prepared in up to 99 % yield and 96 % ee. Noteworthy, CNCOOEt was successfully employed for the first time in the asymmetric Strecker reaction of aldimines and ketimines, affording various α-amino nitriles with excellent yields and ee values (up to >99 % yield and >99 % ee). The merits of current protocol involved facile availability of ligand components, operational simplicity and mild reaction conditions, which made it convenient to prepare synthetically important chiral cyanohydrins and α-amino nitriles. Furthermore, control experiments and NMR analyses were performed to shed light on the catalyst structure. It is indicated that all the hydroxyl groups in cinchona alkaloid and biphenol complex with Ti^IV, forming the catalyst with the structure of (biphenoxide)Ti(OR*)(OiPr). The absolute configuration adopted by biphenol 4 m in the catalyst was identified as S configuration according to the evidence from control experiments and NMR analyses. Moreover, the roles of the protonic additive (iPrOH) and the tertiary amine in the cinchona alkaloid were studied in detail, and the real cyanide reagent in the catalytic cycle was found to be hydrogen cyanide (HCN). Finally, two plausible catalytic cycles were proposed to elucidate the reaction mechanisms.

A highly diastereoselective and enantioselective Michael addition of cyclohexanone, acetone and other ketones to nitroolefins was developed by the use of an amine organocatalyst based on bispidine. Additionally, a theoretical study of transition structures revealed that this bispidine-based primary-secondary amine catalyst could serve through an enamine intermediate and H-bond interaction, which was important for the reactivity and selectivity of this reaction.

The catalytic asymmetric ring opening of meso-epoxides with aromatic amines was achieved using a new proline-based N,N′-dioxide-indium tris(triflate) complex in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee) under mild conditions. The coordination ability of N,N′-dioxide 1c was investigated by X-ray and NMR analysis. A plausible seven-coordinate transition state model was proposed. The chiral N,N′-dioxides surveyed were synthesized from proline through only three conventional steps. The procedure could be run on a gram-scale without any loss of enantioselectivity. This protocol provides a highly practical and useful tool for the bulky preparation of optically pure β-amino alcohols.

The ramipril derivative N,N′-dioxide 3g-indium(III) complex was found to be an efficient catalyst for the allylation of the aromatic α-keto phosphonates. The corresponding α-hydroxy phosphonates were obtained with high yields (up to 98 %) and high enantioselectivities (up to 91 % ee). A bifunctional catalyst system was described with an N-oxide as Lewis base activating tetraallyltin and indium as Lewis acid activating aromatic α-keto phosphonates. A possible catalytic cycle has been proposed to explain the mechanism of the reaction.

An enantioselective Biginelli reaction that proceeds by a dual-activation route has been developed by using a combined catalyst of a readily available trans-4-hydroxyproline-derived secondary amine and a Brønsted acid. Aromatic, heteroaromatic, and fused-ring aldehydes were found to be suitable substrates for this multicomponent reaction. The corresponding dihydropyrimidines were obtained in moderate-to-good yields with up to 98 % ee under mild conditions. Based on the experimental results and the observed absolute configurations of the products, a plausible transition state has been proposed to explain the origin of the activation and the asymmetric induction.

Novel trans-4-hydroxy-L-proline-derived N,N′-dioxides have been developed and used as efficient organocatalysts for the one-pot three-component Strecker reaction with an aldehyde, (1,1-diphenyl)methylamine, and TMSCN. Both aromatic and aliphatic aldehydes were found to be suitable substrates. The corresponding α-amino nitriles were obtained in high yields with up to 95 % ee (ee=enantiomeric excess) under mild conditions. Optically pure products could be obtained after a single recrystallization. The catalyst can be easily prepared from trans-4-hydroxy-L-proline and a diamine in three steps. Based on the experimental results and the observed absolute configurations of the products, a possible transition state has been proposed to explain the origin of the asymmetric induction.